Genetic Variant MAIP1:p.Leu240PhefsTer10 (chr2-199961847-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001394955.1(MAIP1):c.719dupT(p.Leu240PhefsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,613,988 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 7 hom. )

Consequence

MAIP1
NM_001394955.1 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.266

Variant links:

Genes affected

MAIP1 (HGNC:26198): (matrix AAA peptidase interacting protein 1) Predicted to enable ribosome binding activity. Involved in calcium import into the mitochondrion; mitochondrial calcium ion homeostasis; and protein insertion into mitochondrial membrane. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

MAIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-199961847-C-CT is Benign according to our data. Variant chr2-199961847-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 3898234.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000529 (773/1461668) while in subpopulation AMR AF= 0.0162 (724/44714). AF 95% confidence interval is 0.0152. There are 7 homozygotes in gnomad4_exome. There are 312 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAIP1	NM_001394955.1 link	c.719dupT	p.Leu240PhefsTer10	frameshift_variant	Exon 4 of 5	ENST00000392290.6	NP_001381884.1
MAIP1	NM_024520.3 link	c.719dupT	p.Leu240PhefsTer10	frameshift_variant	Exon 5 of 6		NP_078796.2	Q8WWC4A0A024R3U8
MAIP1	NM_001369399.1 link	c.650-1883dupT		intron_variant	Intron 4 of 4		NP_001356328.1
MAIP1	NR_161377.1 link	n.972-116dupT		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAIP1	ENST00000392290.6 link	c.719dupT	p.Leu240PhefsTer10	frameshift_variant	Exon 4 of 5	1	NM_001394955.1	ENSP00000376111.1	Q8WWC4
MAIP1	ENST00000295079.6 link	c.719dupT	p.Leu240PhefsTer10	frameshift_variant	Exon 5 of 6	2		ENSP00000295079.2	Q8WWC4
MAIP1	ENST00000435773.2 link	c.625+1970dupT		intron_variant	Intron 3 of 4	3		ENSP00000396846.2	H7C0V0
MAIP1	ENST00000469156.1 link	n.202-1883dupT		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00238

AC:

599

AN:

251368

Hom.:

AF XY:

0.00179

AC XY:

243

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000529

AC:

773

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

312

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152320

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.00218

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAIP1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over